POS1315 MYCOPHENOLATE USE AND SYSTEMIC SCLEROSIS-ASSOCIATED ESOPHAGEAL DISEASE
Authors: C. He, R. Vasoya, E. Seltzer, J. Menand, M. Silva, V. Courant, A. Leong, E. Olumuyide, H. Verma, D. Qian, S. Lutgen, K. Cavaliere, C. Dobrowolski
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vascular abnormalities in the skin and internal organs, which confers high morbidity and mortality [1]. Esophageal dysmotility (EsD) and gastrointestinal esophageal reflux disease (GERD) are among the most common manifestations of SSc, occurring in up to 80% of patients and decreasing quality of life [2]. To date, treatment of SSc-associated EsD/GERD consists of symptomatic management, including the use of pro-motility agents and anti-reflux medication [3]. Despite the elevated burden of SSc-EsD/GERD, no high-quality evidence to support the use of disease modifying immunomodulatory medications exists. This study explored mycophenolate (MMF), an inosine-5'-monophosphate dehydrogenase inhibitor, which has shown efficacy for suppressing other SSc manifestations including interstitial lung disease and skin thickening [4]. <h3>Objectives</h3> To investigate the potential relationship of MMF with SSc-associated esophageal disease. <h3>Methods</h3> A retrospective chart review was completed for patients with SSc at the Mount Sinai Hospital between January 1, 2000 – January 6, 2022. Individuals with Ssc were identified using a validated ICD-10 M34 code. Data gathered included demographic factors, history of MMF use and cumulative dosing, GERD/EsD diagnosis, medication use, and other relevant clinical factors. Esophageal disease was considered to be present if a patient had any of the following: a formal diagnosis of GERD, absent/ineffective contractility on manometry, or Barrett's esophagus identified on endoscopy. Descriptive statistics were conducted, and X<sup>2</sup> tests/t-tests were computed to compare demographic and outcome variables between patients taking MMF and those not. Multivariable logistic regression analysis was conducted to identify the relationship between MMF use and GERD/EsD prevalence. <h3>Results</h3> 612 participants were included in the study. 167 (27.3%) patients were prescribed MMF, with an average dose of 28.1 g/kg. 141 (84.4%) of the patients prescribed MMF were diagnosed with esophageal disease, compared to 293 (65.9%) patients who were not prescribed MMF (p&lt;0.01). Patients taking MMF were more likely to use a PPI (p&lt;0.01). No differences were found in vascular risk factors (i.e. smoking, coronary artery disease, stroke, hypertension diabetes), head and neck or GI malignancy (thyroid, tongue, gastric, etc.) or presence of psychiatric comorbidities. Multivariable logistic regression revealed that total cumulative MMF dosage (OR=2.99, 95% CI=1.76-5.08, p=&lt;0.0001) was significantly associated with increased likelihood of esophageal disease. <h3>Conclusion</h3> This study revealed that patients with SSc who were prescribed MMF were more likely to have GERD/EsD, and that total cumulative dose of MMF was significantly associated with an increased likelihood of esophageal disease. There are many potential explanations for this result, including possible MMF side effects and bias by indication (i.e. patients taking MMF may have more severe disease to warrant such therapy). Additional studies (notably prospective trials) are needed to examine other possible disease modifying treatments for SSc-associated GERD/EsD. <h3>References</h3> [1]Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017 Oct 7;390(10103):1685-1699. doi: 10.1016/S0140-6736(17)30933-9. Epub 2017 Apr 13. PMID: 28413064. [2]Denaxas K, Ladas SD, Karamanolis GP. Evaluation and management of esophageal manifestations in systemic sclerosis. Ann Gastroenterol. 2018 Mar-Apr;31(2):165-170. doi: 10.20524/aog.2018.0228. Epub 2018 Jan 18. PMID: 29507463; PMCID: PMC5825946. [3]Gyger G, Baron M. Systemic Sclerosis: Gastrointestinal Disease and Its Management. Rheum Dis Clin North Am. 2015 Aug;41(3):459-73. doi: 10.1016/j.rdc.2015.04.007. Epub 2015 May 23. PMID: 26210129. [4]Perelas A, Silver RM, Arrossi AV, Highland KB. Systemic sclerosis-associated interstitial lung disease. Lancet Respir Med. 2020 Mar;8(3):304-320. doi: 10.1016/S2213-2600(19)30480-1. Epub 2020 Feb 27. PMID: 32113575. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.